Recombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns

PURPOSE. Corneal alkali burns are severe ocular injuries characterized by intense inflammation, tissue damage, and vision impairment, with current treatments often insufficient in restoring corneal function and clarity. This study aimed to evaluate the therapeutic effects of recombinant thrombomodulin domain 1 (rTMD1) in the treatment of corneal alkali burns, focusing on its impact on inflammation, tissue repair, fibrosis, and neovascularization. METHODS. A murine model of corneal alkali burn was utilized to investigate the therapeutic potential of rTMD1. The effects of rTMD1 on macrophage polarization, inflammatory response, tissue repair, fibrosis, and neovascularization were assessed through histological analysis, immunohistochemistry, and molecular studies targeting key signaling pathways such as ERK/HIF-1α and vascular endothelial growth factor (VEGF) expression. RESULTS. Administration of rTMD1 significantly modulated macrophage polarization, promoting a transition from the pro-inflammatory M1 phenotype to the reparative M2 phenotype via inhibition of the ERK/HIF-1α pathway. This shift resulted in reduced inflammation, enhanced tissue repair, and controlled fibrosis. Furthermore, rTMD1 inhibited neovascularization by downregulating VEGF expression, aiding in the preservation of corneal clarity. CONCLUSIONS. rTMD1 demonstrates substantial therapeutic potential in treating corneal alkali burns by reducing inflammation, promoting tissue repair, controlling fibrosis, and inhibiting neovascularization. These findings support the further development of rTMD1 as a promising treatment for corneal burns and possibly other inflammatory ocular conditions.